Viral Late domains (L-domains) are short motifs situated within the structural proteins of a number of enveloped viruses that are essential for viral egress. The primary mechanism by which L-domains function involves the binding and recruitment of factors associated with the class E vacuolar protein-sorting (VPS) pathway to sites of viral budding. While VPS proteins responsible for the budding of several viruses including the human immunodeficiency virus (HIV) have been identified, the factors required for release of the Ebola and murine leukemia virus (MLV), utilizing the PPXY-motif L-domain, are not completely defined. The L-domains from these viruses have been shown to bind members of the HECT family of ubiquitin ligases, but how the VPS pathway is then accessed is currently unknown. Recent data has shown that Ebola and MLV can specifically recruit several HECT ligases to the plasma membrane during budding and that the HECT domain coordinates some form of interaction with the class E machinery. This proposal aims to identify the domains and motifs within the HECT ubiquitin ligases that are required for PPXY-dependent viral budding and to discover the cellular factors used by these ligases for recruitment of the VPS pathway. [unreadable] [unreadable] [unreadable]